Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England

Stowe, Julia; Andrews, Nicholas; Kosky, Christopher; Dennis, Gary; Eriksson, Sofia; Hall, Andrew P.; Leschziner, Guy; Reading, Paul; Shneerson, John M.; Donegan, Katherine; Miller, Elizabeth

doi:10.5665/sleep.5752

Cited by 45 publications

(33 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may be a reasonable assumption for well‐defined events with acute onset, such as infections or acute cardiovascular outcomes, but becomes problematic for events with insidious onset as clearly illustrated by this study. This issue has also been considered in other studies of narcolepsy following exposure to the Pandemrix vaccine, and the risk estimate in our study is in general agreement with the findings in other works . The type of diagnosis or event to be studied determines the degree of this potential problem.…”

Section: Discussionsupporting

confidence: 91%

“…This issue has also been considered in other studies of narcolepsy following exposure to the Pandemrix vaccine, and the risk estimate in our study is in general agreement with the findings in other works. 2,3,19 The type of diagnosis or event to be studied determines the degree of this potential problem. In a study validating identification of severe infections in a hospital discharge registry, meningitis could be captured with great accuracy while sepsis proved difficult to identify with any certainty.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Change in risk for narcolepsy over time and impact of definition of onset date following vaccination with AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix) during the 2009 H1N1 influenza pandemic

Granath

Gedeborg

Smedje

et al. 2019

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

Purpose To estimate risk for narcolepsy in defined time windows following exposure to adjuvanted A(H1N1) pandemic vaccine (Pandemrix) and impact of different definitions of index date for the narcolepsy diagnosis. Methods Vaccine exposure in approximately 30% of the Swedish population in 2009 was linked to information on narcolepsy diagnosis retrieved from the national patient registry. Cases were verified by a systematic chart review. Poisson regression was used to compare incidence in defined time windows following vaccination. Results Of 266 cases of narcolepsy identified, 25% (66/266) were prevalent cases with symptom onset documented before vaccine exposure. Incident cases had a median time interval between first symptom and the date recorded in the patient registry of 64 weeks (IQR 39‐107) when vaccinated (N = 182) and 65 weeks (IQR 51‐72) when unvaccinated (N = 16). With first symptom defining index date, the adjusted risk for narcolepsy in younger patients was increased 14 times during the first year after vaccination, three times elevated the second year, but with no detectable increased risk more than 2 years after vaccination exposure. Using the index date from the patient registry, the adjusted increase in risk was about seven times elevated for all three time intervals. Conclusions The magnitude of the estimated increased risk for narcolepsy following exposure to the A(H1N1) pandemic vaccine is highly dependent on the method used to determine the index date for disease onset. The sometimes very long and potentially variable interval from first symptom to a health care registry diagnosis complicates estimations of risk.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Change in risk for narcolepsy over time and impact of definition of onset date following vaccination with AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix) during the 2009 H1N1 influenza pandemic

Granath

Gedeborg

Smedje

et al. 2019

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

show abstract

“…We also found that numbers of excess cases were higher in children and adolescents as compared with adults. These findings are in line with published data …”

Section: Discussionmentioning

confidence: 99%

“…Recently published epidemiological studies conducted in Europe associate an AS03 adjuvanted pandemic influenza vaccine (Pandemrix®, GlaxoSmithKline Biologicals, Dresden, Germany) with narcolepsy. [14][15][16][17][18][19][20][21][22][23][24] Despite intensive worldwide research devoted to investigate how narcolepsy can be induced by immunization with Pandemrix®, the pathomechanism has not been unraveled so far. [25][26][27][28] In Germany, starting from 26 th October 2009, a mass vaccination campaign against pandemic influenza A (H1N1) was conducted with the majority of vaccinees receiving Pandemrix®.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous reporting of suspected narcolepsy after vaccination against pandemic influenza A (H1N1) in Germany

Oberle

Pavel

Keller‐Stanislawski

2017

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

show abstract

“…The vaccination coverage with Pandemrix was high in all of these countries [10-13]. The risk was first noted in children and adolescents, and later also in young adults [13][14][15][16]. The time period for increased risk is still unclear.…”

Section: Epidemiology-how Big Was the Risk Of Pandemrix-related Narcomentioning

confidence: 99%

Narcolepsy Associated with Pandemrix Vaccine

Sarkanen

Alakuijala

Julkunen

et al. 2018

Curr Neurol Neurosci Rep

View full text Add to dashboard Cite

After the Pandemrix vaccination campaign in 2009-2010, the risk of narcolepsy was increased 5- to 14-fold in children and adolescents and 2- to 7-fold in adults. According to observational studies, the risk of narcolepsy was elevated for 2 years after the Pandemrix vaccination. Some confounding factors and potential diagnostic biases may influence the observed narcolepsy risk in some studies, but it is unlikely that they would explain the clearly increased incidence in all the countries where Pandemrix was used. An increased risk of narcolepsy after natural H1N1 infection was reported from China, where pandemic influenza vaccination was not used. There is more and more evidence that narcolepsy is an autoimmune disease. All Pandemrix-associated narcolepsy cases have been positive for HLA class II DQB1*06:02 and novel predisposing genetic factors directly linking to the immune system have been identified. Even though recent studies have identified autoantibodies against multiple neuronal structures and other host proteins and peptides, no specific autoantigens that would explain the disease mechanism in narcolepsy have been identified thus far. There was a marked increase in the incidence of narcolepsy after Pandemrix vaccination, especially in adolescents, but also in young adults and younger children. All vaccine-related cases were of narcolepsy type 1 characterized by hypocretin deficiency in the central nervous system. The disease phenotype and the severity of symptoms varied considerably in children and adolescents suffering from Pandemrix-associated narcolepsy, but they were indistinguishable from the symptoms of idiopathic narcolepsy. Narcolepsy type 1 is most likely an autoimmune disease, but the mechanisms have remained elusive.

show abstract

Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England

Abstract: We found a significantly increased risk of narcolepsy in adults following Pandemrix vaccination in England. The risk was lower than that seen in children using a similar study design.

Cited by 45 publications

References 12 publications

Change in risk for narcolepsy over time and impact of definition of onset date following vaccination with AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix) during the 2009 H1N1 influenza pandemic

Change in risk for narcolepsy over time and impact of definition of onset date following vaccination with AS03 adjuvanted pandemic A/H1N1 influenza vaccine (Pandemrix) during the 2009 H1N1 influenza pandemic

Spontaneous reporting of suspected narcolepsy after vaccination against pandemic influenza A (H1N1) in Germany

Narcolepsy Associated with Pandemrix Vaccine

Contact Info

Product

Resources

About